Artificial Downregulation of Ribosomal Protein L34 Restricts the Proliferation and Metastasis of Colorectal Cancer by Suppressing the JAK2/STAT3 Signaling Pathway
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Yi-Chao Liang1, Rui Li1, Shu-Rui Bao1
1Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, P.R. China.
Abstract:
The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.
Insights
Ribosomal protein L34 (RPL34) promotes colorectal cancer (CRC) growth and metastasis by activating the JAK2/STAT3 pathway and inducing EMT. Its stability is regulated by CAND1, highlighting a new therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant expression of ribosomal protein L34 (RPL34) is implicated in various cancers.
- The specific role of RPL34 in colorectal cancer (CRC) progression remained unclear.
Purpose of the Study:
- To investigate the role of RPL34 in colorectal cancer (CRC) development and progression.
- To identify molecular mechanisms underlying RPL34's function in CRC.
Main Methods:
- Quantitative analysis of RPL34 expression in CRC tissues.
- In vitro and in vivo assays to assess the impact of RPL34 manipulation on CRC cell behavior.
- Western blotting, immunoprecipitation, and cell cycle analysis.
- Investigation of the JAK2/STAT3 signaling pathway and epithelial-to-mesenchymal transition (EMT) markers.
Main Results:
- RPL34 expression was significantly elevated in CRC tissues compared to normal tissues.
- RPL34 overexpression enhanced CRC cell proliferation, migration, invasion, and metastasis.
- RPL34 accelerated cell cycle, activated JAK2/STAT3 signaling, and induced EMT.
- Cullin-associated NEDD8-dissociated protein 1 (CAND1) was identified as an RPL34 interactor, stabilizing RPL34 protein.
- CAND1 overexpression promoted CRC phenotypes and EMT, effects rescued by RPL34 knockdown.
Conclusions:
- RPL34 is a key driver of colorectal cancer (CRC) progression, promoting proliferation and metastasis.
- RPL34 exerts its effects partly through activating the JAK2/STAT3 pathway and inducing EMT.
- CAND1 stabilizes RPL34, contributing to CRC malignancy, suggesting a novel therapeutic target.
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